Studies are in progress to understand further the biochemical and pharmacological basis for the selective effects of antimetabolites, namely, ara-C, F-pyrimidines and deazauridine. These studies include: 1) The ability of tumor and normal cells to utilize purine and pyrimidine de novo and salvage metabolites for nucleic acid synthesis; 2) the extent of metabolic activation and incorporation into nucleic acid of these agents; 3) intracellular retention of the various drug metabolites including the active and inactive components; and 4) The in vivo modulation of the toxicity and antitumor activity of these drugs by normal purine and pyrimidine metabolites. Under conditions of modulation, the effects of these modulators on the pharmacokinetic parameters and on the in vivo drug metabolism is being evaluated in both normal and tumorous tissue.